Pharmacological modulation of endogenous dopamine and DOPAC outflow from nucleus accumbens

The release of endogenous DA and DOPAC from nucleus accumbens slices were studied measuring net outflow of DA and DOPAC in the superfusate of static chambers, to analyze the correlation between DA and DOPAC outflows and identify which DA stores may serve as possible sources for DOPAC formation. Under resting conditions, or following stimulation with low (< 15 mM) KCl concentration, DOPAC outflow was greater than DA. When DA release was stimulated by higher (> 25 mM) KCl concentrations, DA outflow increased, proportionally more than DOPAC. In the virtual absence of Ca2+ in the Krebs solution DA outflow, induced by 25 mM KCl, was reduced to about 10%, while DOPAC outflow was only reduced to 45%. When the synthesis of DA was inhibited with alpha-MPT, DA and DOPAC outflow were unchanged during the first stimulation period. During a second stimulation period, however, their outflow were significantly reduced. Nomifensine, a DA uptake inhibitor, increased the basal DA outflow by about 100%, but only blocked DOPAC basal outflow by about 25%. The 25 mM KCl stimulated DA outflow was not affected by Nomifensine, while the stimulated DOPAC outflow was reduced by about 50%. These results demonstrate that there is a weak correlation between the outflows of DA and DOPAC, suggesting a complex relationship between the mobilization of the different DA pools and DOPAC outflow. The formation of DOPAC from some of these pools, appear to be dependent on the stimulation levels and on the pharmacological manipulation of the tissue.